Factors determining the rate of relaxation of rabbit aortic strips after an exposure to noradrenaline.

1. When noradrenaline distributes exclusively into the: extraneuronal o-methylation of about one third of the extracellular space (i.e., when both, neuronal and extraneuronal uptake mechanisms are blocked by the presence of cocaine and corticosterone), the response of rabbit aortic strips to noradrenaline is concentration-dependent and relaxation curves (obtained during wash out and starting from different heights) are parallel. Under these conditions the "time required for relaxation to 50 or 20% of the initial contraction" (t50 and t20, respectively) is positively correlated with the initial height of contraction. 2. Measurements of the rate of relaxation that are independent of the height of the initial contraction are obtained either by appropriate correction of the t50 (or t20) or by determination of the "average rate of relaxation down to the 25% level of maximum contraction". 3. Relaxation experiments should a) be carried out with initial contractions of less than 75% of maximum and b) use a measure of the rate of relaxation that is independent of the initial height of contraction. 4. When the experimental conditions favour the extraneuronal accumulation of noradrenaline, corticosterone affects the relaxation of the strips in a way which is consistent with the view that efflux of unchanged amine from extraneuronal stores influences the rate of relaxation. 5. When extraneuonal uptake is operative and accumulation of noradrenaline is poor (i.e., when extraneuronal catechol-O-methyl transferase is intact), corticosterone affects relaxation in a way which is consistent with the view that normally the extraneuronal system serves as a site of loss. Under these conditions corticosterone prevented, during the first 5 min of wash out, the extracellularly distributed amine. 6. It is concluded that the experimental conditions of relaxation experiments determine whether the noradrenaline stores serve as a source of efflux of unchanged amine or as a site of loss.